The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway involves a three-step cascade of kinases that transduce signals and promote processes such as cell growth, development, and apoptosis. An aberrant response of this pathway is related to the proliferation of cell diseases and tumors. By using simulation modeling, we document that the protein arginine methyltransferase 5 (PRMT5) modulates the MAPK pathway and thus avoids an aberrant behavior. PRMT5 methylates the Raf kinase, reducing its catalytic activity and thereby, reducing the activation of ERK in time and amplitude.

Two minimal computational models of the epidermal growth factor (EGF)-Ras-ERK MAPK pathway influenced by PRMT5 were proposed: a first model in which PRMT5 is activated by EGF and a second one in which PRMT5 is stimulated by the cascade response. The reported results show that PRMT5 reduces the time duration and the expression of the activated ERK in both cases, but only in the first model PRMT5 limits the EGF range that generates an ERK activation. Based on our data, we propose the protein PRMT5 as a regulatory factor to develop strategies to fight against an excessive activity of the MAPK pathway, which could be of use in chronic diseases and cancer.

细胞外信号调节激酶（ERK）丝裂原激活的蛋白激酶（MAPK）途径涉及三步级联的激酶，这些激酶可转导信号并促进诸如细胞生长，发育和凋亡的过程。该途径的异常反应与细胞疾病和肿瘤的增殖有关。通过使用仿真模型，我们记录了蛋白质精氨酸甲基转移酶5（PRMT5）调节MAPK途径，从而避免异常行为。PRMT5使Raf激酶甲基化，从而降低其催化活性，从而在时间和振幅上降低ERK的活化。

提出了两个受PRMT5影响的表皮生长因子（EGF）-Ras-ERK MAPK途径的最小计算模型：第一个模型由EGF激活PRMT5，第二个模型由级联反应刺激PRMT5。报告的结果表明，在两种情况下，PRMT5均会减少持续时间和激活的ERK的表达，但仅在第一个模型中，PRMT5会限制产生ERK激活的EGF范围。根据我们的数据，我们提出蛋白质PRMT5作为调节因子，以开发策略来对抗MAPK途径的过度活性，该活性可能在慢性疾病和癌症中有用。